Uray Karen S, Laine Glen A, Xue Hasan, Allen Steven J, Cox Charles S
Division of Pediatric Surgery, Department of Surgery, University of Texas Medical School at Houston, 6431 Fannin, Houston, TX 77030, USA.
Shock. 2007 Aug;28(2):239-44. doi: 10.1097/shk.0b013e318033eaae.
Increased signal transducer and activator of transcription 3 (STAT3) activation has been shown to be associated with intestinal dysfunction. The purpose of this study was to investigate the role of STAT3 in edema-induced intestinal dysfunction. Intestinal edema was induced in male Sprague-Dawley rats by a combination of mesenteric venous hypertension and fluid resuscitation (RESUS + VH). Resuscitation fluid alone (RESUS), venous hypertension alone (VH), and sham-operated rats (CONTROL) were used as controls. Edema development, STAT3 DNA binding activity, nuclear translocation, and phosphorylation were measured in rat distal small intestinal muscularis. A significant amount of edema development was measured in the RESUS + VH rats compared with CONTROL and VH from 30 min to 6 h after surgery. Edema developed in the RESUS group at 30 min postsurgery but resolved before 2 h postsurgery. A significant increase in STAT3 DNA binding activity was observed from 30 min to 6 h after surgery in the edematous RESUS + VH group compared with nonedematous CONTROL. In addition, a significant increase in STAT3 nuclear translocation and phosphorylation was measured in the RESUS + VH group 2 and 6 h after surgery. No significant increases in STAT3 activation were observed in either the RESUS or VH groups compared with CONTROL. Rats in both the RESUS + VH and CONTROL groups were pretreated with AG490 (5 mg/kg, i.p.) to block STAT3 activation. Signal transducer and activator of transcription 3 inhibition attenuated edema-induced decrease in intestinal contractile activity and myosin light chain phosphorylation. We conclude from these data that edema-induced decreases in intestinal contractile activity are mediated, at least in part, by STAT3 activation.
信号转导与转录激活因子3（STAT3）激活增加已被证明与肠道功能障碍有关。本研究的目的是探讨STAT3在水肿诱导的肠道功能障碍中的作用。通过肠系膜静脉高压和液体复苏（RESUS + VH）联合诱导雄性Sprague-Dawley大鼠发生肠道水肿。单独的复苏液（RESUS）、单独的静脉高压（VH）以及假手术大鼠（CONTROL）作为对照。测量大鼠远端小肠肌层的水肿发展、STAT3 DNA结合活性、核转位和磷酸化。与对照组和VH组相比，RESUS + VH组在术后30分钟至6小时测量到大量水肿发展。RESUS组在术后30分钟出现水肿，但在术后2小时前消退。与无水肿的对照组相比，水肿的RESUS + VH组在术后30分钟至6小时观察到STAT3 DNA结合活性显著增加。此外，RESUS + VH组在术后2小时和6小时测量到STAT3核转位和磷酸化显著增加。与对照组相比，RESUS组和VH组均未观察到STAT3激活的显著增加。RESUS + VH组和对照组的大鼠均用AG490（5 mg/kg，腹腔注射）预处理以阻断STAT3激活。信号转导与转录激活因子3抑制减弱了水肿诱导的肠道收缩活性降低和肌球蛋白轻链磷酸化。我们从这些数据得出结论，水肿诱导的肠道收缩活性降低至少部分是由STAT3激活介导的。
